The Division of Cardiology at the University of Texas Southwestern Medical Center (Core) seeks to expand its research in complex vascular disease. To this end, we are actively recruiting a newly independent investigator (NIl), Santhi Ganesh, MD, from the NHLBI to facilitate our growth in this area. Since the completion of the Human Genome Project in 2003 and the International HapMap Project in -2005, there has been a rapid expansion in genetic technologies aimed to understand complex-human diseases, including high-density single nucleotide polymorphism (SNP) genotyping for case-control and population-based association testing and sequencing. The application of these genetic methods through genome-wide association studies (GWAS) has led to an unprecedented number of novel associations with cardiovascular diseases, with over 200 such associations reported. Currently, a major knowledge gap is lack of understanding of the impact of these associations in terms of the predictive utility of common variants and in terms of the functional relevance of genetic associations. Moving forward, we propose to pursue investigation under the direction of Dr. Ganesh to decipher the biologic consequences of variation in genetic loci associated with human vascular disease. We have identified a core group of collaborators and mentors who will work with Dr. Ganesh in the launch of her program of independent research. Further, our Division/Core has made a major commitment to Dr. Ganesh's success, including plans to support her beyond the two-year funding period proposed here. In summary, we propose a well orchestrated plan of investigation and career development which is at once tailored to the NIl's specific needs and to the emergence of new, multidisciplinary programs of research within our Division/Core.